CYP2S1, a member of the cytochrome P450 superfamily, is located in chromosome 19q13.2 within a cluster with other CYP2 family members [2]. It is inducible by dioxin, coal tar, etc., through the Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Nuclear Translocator (ARNT). CYP2S1 is expressed in epithelial cells of many extrahepatic tissues like respiratory, gastrointestinal, and urinary tracts, and skin. It may metabolize toxic and carcinogenic compounds, as well as endogenous substrates such as retinoic acid, and is thus relevant for human health [2].

In various disease-related studies, in high-altitude pulmonary edema (HAPE) patients, abnormal methylation was found in several CpG sites in the promoter regions of CYP2S1 gene, and its methylation level could predict the risk of HAPE [1]. In psoriasis, CYP2S1 might inhibit keratinocyte proliferation and modulate immune response [3]. In BRAFV600E-driven thyroid cancers, CYP2S1 is a synthetic lethal partner of BRAFV600E, and knockdown of CYP2S1 selectively affects the behaviors of BRAFV600E-mutated thyroid cancer cells [4]. In breast cancer, low cytoplasmic CYP2S1 is associated with adverse breast cancer-specific survival [5]. In lung cancer, knockdown of CYP2S1 inhibits cell proliferation, invasion, migration in vitro and in vivo, and high CYP2S1 expression is an unfavorable prognostic marker [6]. In anti-tuberculosis drug-induced liver injury, CYP2S1 rs338599 polymorphism confers reduced risk and may be a novel marker for risk prediction [7]. In colorectal cancer, CYP2S1 knockdown promotes cell proliferation through increasing PGE2 level, which activates β-catenin signaling, and also increases tumor growth in xenograft mouse model [8].

In conclusion, CYP2S1 plays important roles in multiple disease conditions, including HAPE, psoriasis, thyroid cancer, breast cancer, lung cancer, anti-tuberculosis drug-induced liver injury, and colorectal cancer. These functions are related to processes like cell proliferation, immune response, and disease-specific risk prediction. Studies on CYP2S1, especially those using knockdown models in different cell lines and animal models, help to understand its functions in disease-related biological processes, providing potential directions for disease diagnosis, prognosis, and treatment.